Effects of antihypertensive therapy on intrarenal angiotensin and bradykinin levels in experimental renal insufficiency

Abstract

Whereas angiotensin converting enzyme inhibitors and angiotensin type 1 receptor antagonists have beneficial effects in the remnant model of renal failure, calcium channel blockers do not consistently improve renal disease in this model. This study examined whether these different means of blood pressure reduction have different effects on renal levels of angiotensin (Ang) and bradykinin peptides. Rats subjected to five-sixths nephrectomy were divided into groups with similar hypertension and proteinuria at 4 to 5 weeks. They then received either no treatment, or enalapril, losartan or nifedipine for 2 weeks. Following repeat measurements of proteinuria and blood pressure, Ang II and bradykinin peptides were measured in the remnant kidney and renin, Ang II, and aldosterone were measured in the plasma. All three drugs had equivalent blood pressure-lowering effects. Enalapril and losartan reduced proteinuria but nifedipine did not. Reduction of proteinuria in rats treated with enalapril and losartan was associated with a reduction in Ang II levels in both the peri-infarct and intact portions of the remnant kidney. By contrast, nifedipine increased Ang II levels in the intact portion of the remnant kidney. Losartan reduced bradykinin levels in the peri-infarct portion of the remnant kidney while enalapril reduced bradykinin levels in the intact portion of the remnant kidney. Nifedipine had no effect on intrarenal bradykinin levels. The differential effects of enalapril, losartan and nifedipine on proteinuria and intrarenal Ang II and bradykinin levels suggest that the ability of an antihypertensive to decrease proteinuria may depend on its ability to decrease kidney Ang II and bradykinin levels.